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Titolo:
Modifications of the serotonergic system in mice lacking serotonin transporters: An in vivo electrophysiological study
Autore:
Gobbi, G; Murphy, DL; Lesch, KP; Blier, P;
Indirizzi:
Univ Florida, Inst Brain, Dept Psychiat, Gainesville, FL 32610 USA Univ Florida Gainesville FL USA 32610 Psychiat, Gainesville, FL 32610 USA McGill Univ, Dept Psychiat, Neurobiol Psychiat Unit, Montreal, PQ, Canada McGill Univ Montreal PQ Canada obiol Psychiat Unit, Montreal, PQ, Canada NIMH, Clin Sci Lab, Bethesda, MD 20892 USA NIMH Bethesda MD USA 20892NIMH, Clin Sci Lab, Bethesda, MD 20892 USA Univ Wurzburg, Dept Psychiat, D-8700 Wurzburg, Germany Univ Wurzburg Wurzburg Germany D-8700 Psychiat, D-8700 Wurzburg, Germany
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 3, volume: 296, anno: 2001,
pagine: 987 - 995
SICI:
0022-3565(200103)296:3<987:MOTSSI>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
DORSAL RAPHE NEURONS; HIPPOCAMPAL PYRAMIDAL CELLS; NEUROENDOCRINE RESPONSES; 5-HT NEUROTRANSMISSION; KNOCKOUT MICE; RECEPTORS; RAT; DESENSITIZATION; FLUOXETINE; PAROXETINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Blier, P Univ Florida, Inst Brain, Dept Psychiat, POB 100256, Gainesville,FL 32610USA Univ Florida POB 100256 Gainesville FL USA 32610 lle, FL 32610USA
Citazione:
G. Gobbi et al., "Modifications of the serotonergic system in mice lacking serotonin transporters: An in vivo electrophysiological study", J PHARM EXP, 296(3), 2001, pp. 987-995

Abstract

The serotonin transporter (5-HTT) plays a key role in the regulation of serotonin (5-hydroxytryptamine, 5-HT) transmission in the pathophysiology andtherapeutics of several psychiatric disorders. The mean spontaneous firingrate of midbrain dorsal raphe 5-HT neurons was recorded in chloral hydrate-anesthetized mice. The serotonin transporter (5-HTT), which plays a key role in the regulation of serotonin was significantly decreased in homozygousmice lacking the 5-HT transporter (5-HTT-/-) by 66% and in heterozygous (5-HTT +/-) mice by 36% compared with their normal littermates (5-HTT +/-). Systemic injection of the selective 5-HT1A receptor antagonist WAY 100635 enhanced 5-HT neuronal firing by 127% in 5-HT -/- mice, thus indicating an enhanced synaptic availability of 5-HT at inhibitory 5-HT1A receptors. Nevertheless, the cell body 5-HT1A autoreceptors were desensitized in both 5-HTT -/- and 5-HTT +/- mice. At the postsynaptic level, the recovery time (RT50)of the firing rate of hippocampus CA(3) pyramidal neurons following iontophoretic applications of 5-HT was significantly prolonged only in 5-HTT -/- mice. The selective 5-HT reuptake inhibitor paroxetine significantly prolonged the RT50 in 5-HTT +/+ and 5-HTT +/- mice, without altering the maximal inhibitory effect of 5-HT. These neurons in 5-HTT -/- mice showed an attenuated response to the 5-HT1A agonist 8-hydroxy-2-diproplyaminotetralin, but not to 5-HT itself. These results establish that the lack of 5-HTT causes a prolonged recovery of firing activity following 5-HT applications. The genetic deletion of the 5-HTT plays a key role on 5-HT1A receptor adaptation: adesensitization at pre- and postsynaptic levels in 5-HTT -/- mice, but to a different extent, and only at the presynaptic level in the 5-HTT +/- group.

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Documento generato il 04/04/20 alle ore 02:27:19